The effects of i.v. 1,25-dihydroxycholecalciferol (DHCC) on blood pressure and insulin sensitivity were studied in 7 patients on maintenance hemodialysis and compared with 7 healthy controls. Three days after discontinuing oral 1,25-DHCC, the dialysis patients were evaluated by glucose clamp studies to quantitate insulin sensitivity, with (+D) and without (−D) a prior single dose of i.v. 1,25-DHCC at 2μg/m2. Blood pressure was measured just before the glucose studies. During −D studies, the patients were hypertensive (mean arterial blood pressure 108±2 mmHg, controls 84±4 mmHg,P<0.02) and insulin resistant (insulin sensitivity index 7.5±0.4 mg/kg·min per μU per ml, controls 14.2±0.7,P<0.01) i.v. 1,25-DHCC significantly reduced the mean arterial blood pressure (96±3 mmHg,P<0.05) and increased insulin sensivity (10.9±0.5 mg/kg·min per μU per ml,P<0.02) in the dialysis patients. I. V. 1,25-DHCC did not change blood pressure and insulin sensitivity in the control subjects. During −D studies, serum concentrations of 1,25-DHCC were significantly lower in patients than controls (P<0.02). Serum 1,25-DHCC during the +D studies increased to supraphysiological levels in both patients and controls. Serum concentrations of intact parathyroid hormone, total and ionized calcium, magnesium, potassium, urea nitrogen and creatinine were not different between the +D and −D studies in either the dialysis patients or the controls. These results suggest that pharmacological doses of 1,25-DHCC may have therapeutic value in the treatment of hypertension and insulin resistance in dialysis patients.